PMID- 26776487 OWN - NLM STAT- MEDLINE DCOM- 20161028 LR - 20231111 IS - 1460-4744 (Electronic) IS - 0306-0012 (Print) IS - 0306-0012 (Linking) VI - 45 IP - 5 DP - 2016 Mar 7 TI - Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. PG - 1457-501 LID - 10.1039/c5cs00798d [doi] AB - New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart" MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications. FAU - Karimi, Mahdi AU - Karimi M AD - Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. FAU - Ghasemi, Amir AU - Ghasemi A AD - Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran. FAU - Sahandi Zangabad, Parham AU - Sahandi Zangabad P AD - Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran. FAU - Rahighi, Reza AU - Rahighi R AD - Department of Research and Development, Sharif Ultrahigh Nanotechnologists (SUN) Company, P.O. Box: 13488-96394, Tehran, Iran and Nanotechnology Research Center, Research Institute of Petroleum Industry (RIPI), West Entrance Blvd., Olympic Village, P.O. Box: 14857-33111, Tehran, Iran. FAU - Moosavi Basri, S Masoud AU - Moosavi Basri SM AD - Bioenvironmental Research Center, Sharif University of Technology, Tehran, Iran and Civil & Environmental Engineering Department, Shahid Beheshti University, Tehran, Iran. FAU - Mirshekari, H AU - Mirshekari H AD - Department of Biotechnology, University of Kerala, Trivandrum, India. FAU - Amiri, M AU - Amiri M AD - Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran. FAU - Shafaei Pishabad, Z AU - Shafaei Pishabad Z AD - Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran. FAU - Aslani, A AU - Aslani A AD - Department of Materials Science and Engineering, Sharif University of Technology, 11365-9466, Tehran, Iran. FAU - Bozorgomid, M AU - Bozorgomid M AD - Department of Applied Chemistry, Central Branch of Islamic Azad University of Tehran, Tehran, Iran. FAU - Ghosh, D AU - Ghosh D AD - Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, Tehran, Iran. FAU - Beyzavi, A AU - Beyzavi A AD - School of Mechanical Engineering, Boston University, Boston, MA, USA. FAU - Vaseghi, A AU - Vaseghi A AD - Department of Biotechnology, Faculty of Advanced Science and Technologies of Isfahan, Isfahan, Iran. FAU - Aref, A R AU - Aref AR AD - Department of Cancer Biology, Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Department of Genetics, Harvard Medical School, Boston, MA 02215, USA. FAU - Haghani, L AU - Haghani L AD - School of Medicine, International Campus of Tehran University of Medical Science, Tehran, Iran. FAU - Bahrami, S AU - Bahrami S AD - Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. FAU - Hamblin, Michael R AU - Hamblin MR AD - Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA. Hamblin@helix.mgh.harvard.edu and Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA and Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA. LA - eng GR - R01 AI050875/AI/NIAID NIH HHS/United States GR - R01AI050875/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review PL - England TA - Chem Soc Rev JT - Chemical Society reviews JID - 0335405 RN - 0 (Drug Carriers) RN - 0 (Micelles) RN - 0 (Pharmaceutical Preparations) RN - 9007-49-2 (DNA) SB - IM MH - DNA/*administration & dosage/chemistry MH - Drug Carriers/*chemistry MH - *Drug Delivery Systems MH - Hydrogen-Ion Concentration MH - Micelles MH - Nanoparticles/*chemistry MH - Pharmaceutical Preparations/*administration & dosage/chemistry PMC - PMC4775468 MID - NIHMS755363 EDAT- 2016/01/19 06:00 MHDA- 2016/11/01 06:00 PMCR- 2017/03/07 CRDT- 2016/01/19 06:00 PHST- 2016/01/19 06:00 [entrez] PHST- 2016/01/19 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] PHST- 2017/03/07 00:00 [pmc-release] AID - 10.1039/c5cs00798d [doi] PST - ppublish SO - Chem Soc Rev. 2016 Mar 7;45(5):1457-501. doi: 10.1039/c5cs00798d.